POS1122 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS AND AN INADEQUATE RESPONSE TO BIOLOGIC DMARD THERAPY: ONE-YEAR RESULTS FROM A PHASE 3 STUDY
Authors: X. Baraliakos, D. Van der Heijde, J. Sieper, R. Inman, H. Kameda, Y. LI, X. Bu, A. Shmagel, P. Wung, I. H. Song, A. Deodhar
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Upadacitinib (UPA), a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients (pts) with ankylosing spondylitis (AS) in the phase 3 SELECT-AXIS 1 and 2 program, including pts with an inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARD-IR).<sup>[1,2]</sup> <h3>Objectives</h3> To assess the 1-year efficacy and safety of UPA 15 mg once daily (QD) in bDMARD-IR pts with active AS in SELECT-AXIS 2. <h3>Methods</h3> The design of the SELECT-AXIS 2 AS bDMARD-IR study has been described previously.<sup>[1]</sup> Pts who completed the 14-wk placebo (PBO)-controlled period were eligible to enter an ongoing long-term extension and receive open-label UPA 15 mg QD for up to 90 wks. This analysis evaluated efficacy over 52 wks in pts who received continuous UPA, and those who switched from PBO to UPA at wk 14. Efficacy endpoints included proportion of pts achieving Assessment of SpondyloArthritis international Society 40 response (ASAS40), ASAS partial remission (PR), ASDAS (AS Disease Activity Score with C-reactive protein [CRP]) low disease activity (LDA; &lt;2.1), ASDAS inactive disease (ID; &lt;1.3), and changes from baseline in ASDAS and high-sensitivity CRP (hsCRP). As-observed (AO) and non-responder imputation with multiple imputation (NRI-MI) analyses are presented for binary endpoints and mixed model for repeated measures (MMRM) analyses for continuous endpoints. Safety was assessed through the cut-off date of May 19, 2022 in all pts who received ≥1 dose of UPA. Treatment-emergent adverse events (TEAEs) and TEAEs of special interest are presented as exposure-adjusted event rates (events/100 pt-years [E/100 PY]). <h3>Results</h3> A total of 420 pts were randomized and received study drug (PBO to UPA: n=209; continuous UPA: n=211). Response rates were maintained from wk 14 to wk 52 in the continuous UPA group, and responses were similar in the PBO to UPA group at wk 52. NRI-MI response rates at wk 52 for the PBO to UPA and continuous UPA groups, respectively, were: ASAS40 (64.6% and 65.9%), ASAS PR (29.2% and 30.3%), ASDAS LDA (55.3% and 56.9%), and ASDAS ID (25.2% and 26.0%) (<b>Figure 1</b>). Changes from baseline in ASDAS and hsCRP were also similar between groups (-1.9 and -2.0, and -10.6 and -10.0 for the PBO to UPA and continuous UPA groups, respectively). Safety was assessed in 414 pts (534.4 PY of exposure) who received ≥1 dose of UPA (<b>Table 1</b>). Rates of serious TEAEs and TEAEs leading to study drug discontinuation were 9.9 and 3.0 E/100 PY, respectively. Rates of malignancy, major adverse cardiovascular events, and venous thromboembolic events were low (0.2, 0.2, and 0.4 E/100 PY, respectively). <h3>Conclusion</h3> UPA 15 mg demonstrated sustained efficacy up to wk 52 in bDMARD-IR pts with active AS. Similar efficacy was observed at wk 52 in pts with continuous UPA exposure and those who switched from PBO to UPA. UPA 15 mg was generally well tolerated in this bDMARD-IR population, with no new safety signals identified. <h3>References</h3> [1]van der Heijde D, et al. Lancet 2019;394:2108–2117. [2]van der Heijde D, et al. Ann Rheum Dis 2022;81:1515–1523. <h3>Acknowledgements</h3> AbbVie funded this trial and participated in the trial design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. <h3>Disclosure of Interests</h3> Xenofon Baraliakos Speakers bureau: AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, Bristol Myers Squibb, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, and UCB, Désirée van der Heijde Consultant of: AbbVie, Bayer, Bristol Myers Squibb, Cyxone, Eisai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology, Joachim Sieper Speakers bureau: AbbVie, Merck, and Novartis, Consultant of: AbbVie, Merck, Novartis, and UCB, Grant/research support from: AbbVie, Merck, and UCB, Robert Inman Consultant of: AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and Sandoz, Grant/research support from: AbbVie, Amgen, Janssen, and Novartis, Hideto Kameda Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol Myers Squibb, Chugai, Eisai, Gilead, Janssen, Lilly, Mitsubishi Tanabe, Novartis, Pfizer, Sanofi, and UCB, Consultant of: AbbVie, Asahi Kasei, Astellas, Bristol Myers Squibb, Chugai, Eisai, Gilead, Janssen, Lilly, Mitsubishi Tanabe, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Asahi Kasei, Chugai, Eisai, Mitsubishi Tanabe, and Taisho, Yihan Li Employee of: AbbVie, may own stock or options, Xianwei Bu Employee of: AbbVie, may own stock or options, Anna Shmagel Employee of: AbbVie, may own stock or options, Peter Wung Employee of: AbbVie, may own stock or options, In-Ho Song Employee of: AbbVie, may own stock or options, Atul Deodhar Speakers bureau: AbbVie, Amgen, Aurinia, BMS, Celgene, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Celgene, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB.